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. 2009 Dec 30:8:65.
doi: 10.1186/1475-2840-8-65.

Aminoguanidine inhibits aortic hydrogen peroxide production, VSMC NOX activity and hypercontractility in diabetic mice

Jeong-Ho Oak  1 , Ji-Youn Youn, Hua Cai
Affiliations

Aminoguanidine inhibits aortic hydrogen peroxide production, VSMC NOX activity and hypercontractility in diabetic mice

Jeong-Ho Oak et al. Cardiovasc Diabetol. .

Abstract

Background: Dysfunctionally uncoupled endothelial nitric oxide synthase (eNOS) is involved in producing reactive oxygen species (ROS) in the diabetic endothelium. The present study investigated whether anti-diabetes drug Aminoguanidine (AG) has any effect on eNOS function and vascular oxidant stress.

Methods and results: Blood glucose levels were increased to 452.0 +/- 15.1 mg/dl in STZ-treated male C57BL/6J mice (148.4 +/- 3.2 mg/dl in untreated controls). Aortic productions of NO* and O(2)*- were measured specifically and sensitively using electron spin resonance. Diabetic mice had a marked increase in aortic O(2)*- production. Aortic hydrogen peroxide (H(2)O(2)) production was also increased in diabetic aortas and significantly attenuated by AG. AG however had only a marginal effect in reducing aortic O(2)*- production, which corresponded to a minimal effect in improving aortic nitric oxide (NO*) bioavailability. The endothelium-dependent vasodilatation however was modestly but significantly improved by AG, likely consequent to AG-induced reduction in hyper-contractility. NAD(P)H oxidase (NOX)-dependent O(2)*- production was completely attenuated by AG in endothelium-denuded diabetic aortas.

Conclusion: In summary, despite that AG is not an effective eNOS recoupling agent presumably consequent to its ineffectiveness in preventing endothelial NOX activation, it is inhibitory of aortic H(2)O(2) production, VSMC NOX activity, and hypercontractility in diabetes.

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Figures

Figure 1
Figure 1
Effects of AG on aortic superoxide (O2•-) production. A: Representative spectra for aortic O2•- detected by ESR. Freshly isolated aortic segments (~3 mm) were incubated with spin trapping solution and then analyzed using ESR. B: Grouped data of aortic O2•- production expressed as nmol/L per min per mg wet weight. Data are presented as mean ± SEM, n = 6-8.
Figure 2
Figure 2
Effects of AG on aortic hydrogen peroxide (H2O2) production. Total aortic H2O2 production by Amplex Red Assay. Data are presented as mean ± SEM, n = 8.
Figure 3
Figure 3
Effects of AG on aortic nitric oxide (NO•) bioavailability in diabetes. A: Representative ESR spectra for NO•; B: Grouped data of bioavailable NO•. Data are presented as mean ± SEM, n = 6.
Figure 4
Figure 4
Effects of AG on vascular reactivity. A: AG partially restored endothelium-dependent vasorelaxation. B: AG diminished diabetes induced aortic hypercontractility. Data are presented as mean ± SEM, n = 6.
Figure 5
Figure 5
Effects of AG on NOX-sensitive superoxide (O2•-) production. A: NSC23766-sensitive O2•- production from intact aortas B: NSC23766-sensitive O2•- production from endothelium denuded aortas. Data are presented as mean ± SEM, n = 6.
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References

    1. Laing SP, Swerdlow AJ, Slater SD, Burden AC, Morris A, Waugh NR, Gatling W, Bingley PJ, Patterson CC. Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia. 2003;46(6):760–765. doi: 10.1007/s00125-003-1116-6. - DOI - PubMed
    1. Paterson AD, Rutledge BN, Cleary PA, Lachin JM, Crow RS. The effect of intensive diabetes treatment on resting heart rate in type 1 diabetes: the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Diabetes Care. 2007;30(8):2107–2112. doi: 10.2337/dc06-1441. - DOI - PMC - PubMed
    1. Goth L, Eaton JW. Hereditary catalase deficiencies and increased risk of diabetes. Lancet. 2000;356(9244):1820–1821. doi: 10.1016/S0140-6736(00)03238-4. - DOI - PubMed
    1. Rosen P, Nawroth PP, King G, Moller W, Tritschler HJ, Packer L. The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab Res Rev. 2001;17(3):189–212. doi: 10.1002/dmrr.196. - DOI - PubMed
    1. Sakai K, Matsumoto K, Nishikawa T, Suefuji M, Nakamaru K, Hirashima Y, Kawashima J, Shirotani T, Ichinose K, Brownlee M. Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic beta-cells. Biochem Biophys Res Commun. 2003;300(1):216–222. doi: 10.1016/S0006-291X(02)02832-2. - DOI - PubMed

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